1. Technical Field of the Invention
The present invention relates to the formulation of an antagonist of CGRP (peptide derived from the calcitonin gene: Calcitonin Gene Related Peptide, or "CGRP") into topically applicable cosmetic/pharmaceutical/dermatological compositions, for the treatment of sensitive skin-types, as well as to cosmetic compositions containing a CGRP antagonist for reducing or eliminating the irritant effects elicited by certain active agents, and especially by certain bioactive agents conventionally employed in the cosmetics, pharmaceutical or dermatological field.
2. Description of the Prior Art
It is known to this art that certain skin-types are more sensitive than others. The symptoms of sensitive skin-types were heretofore poorly characterized and the problem of these skin-types was, as a result, poorly defined; the exact mechanism involved in the sensitivity--nonallergic cutaneous hyperreactivity--of the skin, was unknown. In certain quarters it was believed that a sensitive skin was a skin which reacted to cosmetic products, while others believed that it concerned a skin which reacted to a variety of external factors, not necessarily associated with cosmetic products.
Certain tests have been conducted in attempting to define sensitive skin-types, for example tests using lactic acid and DMSO which are known to be irritant substances: see, for example, the article by K. Lammintausta et al, Dermatoses, 36, pages 45-49 (1988); and the article by T. Agner and J. Serup, Clinical and Experimental Dermatology, 14, pages 214-217 (1989). However, these tests did not make it possible to characterize sensitive skin-types.
Moreover, sensitive skin-types were likened to allergic skin-types.
Taking account of the ignorance of the characteristics of sensitive skin-types, it was hitherto very difficult to treat them and they were treated indirectly, for example by limiting, in the cosmetic compositions, active species eliciting an irritant effect, such as surfactants, preservatives or perfumes, as well as certain otherwise bioactive agents.
The assignee hereof has now conducted many clinical tests and has been able to determine the symptoms associated with sensitive skin-types. These symptoms are, in particular, subjective signs, which are essentially dysaesthesic sensations. By the term "dysaesthesic sensations" are intended more or less painful sensations experienced in an area of the skin, such as stinging, tingling, itching or pruritus, burning, inflammation, discomfort, pulling, etc.
The assignee hereof has also been able to demonstrate that a sensitive skin-type is not an allergic skin-type. Indeed, an allergic skin-type is a skin-type which reacts to an external agent, an allergen, which triggers an allergic reaction. This is an immunological process which takes place only when an allergen is present and which affects only sensitized individuals. To the contrary, the essential characteristic of sensitive skin, according to the assignee hereof, is a mechanism of response to external factors, which may be the case for any individual, even if the individuals said to have sensitive skin react faster thereto than the other individuals. This is a nonspecific mechanism and not an immunological one.
It has now been determined that sensitive skin-types can be divided into two major clinical forms; irritable and/or reactive skin-types and intolerant skin-types.
An irritable and/or reactive skin-type is a skin-type which reacts by a pruritus, i.e., by itching, or by stinging, to various factors such as the environment, emotions, foods, the wind, rubbing, shaving, soap, surfactants, hard water having a high calcium concentration, temperature variations or wool. In general, these signs are associated with a dry skin with or without dartres, or with a skin which displays an erythema.
An intolerant skin-type is a skin-type which reacts, by sensations of inflammation, pulling, tingling and/or redness, to various factors such as the environment, emotions and foods. In general, these signs are associated with a hyperseborrhoeic or acneic skin-type with or without dartres, and with an erythema.
"Sensitive" scalps have a more unequivocal clinical semeiology: the sensations of pruritus and/or of stinging and/or of inflammation are essentially triggered by local factors such as rubbing, soap, surfactants, hard water with a high calcium concentration, shampoos or lotions. These sensations are also sometimes triggered by factors such as the environment, emotions and/or foods. Erythema and hyperseborrhoea of the scalp and the presence of dandruff are often associated with the above signs.
Moreover, in certain anatomical regions such as the major folds (groin, genital, axillary, popliteal, anal and submammary regions, and in the crook of the elbow) and the feet, sensitive skin is reflected in pruriginous sensations and/or dysaesthesic sensations (inflammation, stinging) associated in particular with sweat, rubbing, wool, surfactants, hard water with a high calcium concentration and/or temperature variations.
The assignee hereof has also now developed a test in order to determine whether or not a skin-type is sensitive. Indeed, after having carried out a multitude of tests for the purpose of defining sensitive skin, it has now surprisingly been found that there is a nexus between individuals with sensitive skin and those who react to a topical application of capsaicin.
The capsaicin test entails applying, to about 4 cm.sup.2 of skin, 0.05 ml of a cream containing 0.075% of capsaicin and in noting the appearance of subjective signs induced by this application, such as stinging, burning and itching. In individuals having sensitive skin, these signs appear between 3 and 20 minutes after application and are succeeded by the appearance of an erythema which begins at the edge of the zone of application.
Hitherto, capsaicin was used as a medicinal active agent, in particular for treating zona pains. Capsaicin induces a release of neuropeptides from sensitive nerve fibers, and in particular of CGRP which originates from epidermal and dermal nerve endings. It has been observed that the physiopathological pattern common to the conditions of sensitive skin-types was associated with a marked ability to release neuropeptides, and more particularly CGRP, into the skin. The dysaesthesic manifestations which are induced by their release are referred to as "neurogenic."
CGRP is a polypeptide chemical species produced and released by a nerve ending. CGRP is involved, in particular, in respiratory and inflammatory diseases, in allergic diseases and in certain dermatological diseases such as eczema or prurigo.